Net Effect Research Articles

The impact and effectiveness of China’s entrepreneurship policy for back-home migrant workers

This study aims to estimate the net effect of China’s entrepreneurship policy on back-home migrant workers since 2015. Using survey data from the provinces of; Zhejiang, Henan, and Guizhou with propensity score matching to control selection bias, the study indicates that the overall entrepreneurship policy has a significant positive impact on the probability of entrepreneurial entry. The poverty alleviation effect of the overall policy is greater than its industrial development effect, while the employment effect is not significant. The infrastructure policy’s effect on employment, industrial development, and poverty alleviation is greater than the other policies, and the financial policy’s effect on these three aspects is not significant. This study contributes to the existing literature by addressing a well-defined gap regarding the net effect of entrepreneurship policy on entrepreneurship entry and provides well-supported and plausible explanations for the inconsistencies among previous studies on policy effect indicators. As a practical contribution, this study provides China and other developing economies with compelling empirical evidence to support the design and amendment of entrepreneurship policy at the national level.

Stream hydrology controls on ice cliff evolution and survival on debris-covered glaciers

Abstract. Ice cliffs are melt hot spots that contribute disproportionately to melt on debris-covered glaciers. In this study, we investigate the impact of supraglacial stream hydrology on ice cliffs using in situ and remote sensing observations, streamflow measurements, and a conceptual geomorphic model of ice cliff backwasting applied to ice cliffs on Kennicott Glacier, Alaska. We found that 33 % of ice cliffs (accounting for 69 % of the ice cliff area) are actively influenced by streams, while half are nearer than 10 m from the nearest stream. Supraglacial streams contribute to ice cliff formation and maintenance by horizontal meandering, vertical incision, and debris transport. These processes produce an undercut lip at the ice cliff base and transport clasts up to tens of centimeters in diameter, preventing reburial of ice cliffs by debris. Stream meander morphology reminiscent of sedimentary river channel meanders and oxbow lakes produces sinuous and crescent ice cliff shapes. Stream avulsions result in rapid ice cliff collapse and local channel abandonment. Ice cliffs abandoned by streams are observed to be reburied by supraglacial debris, indicating a strong role played by streams in ice cliff persistence. We also report on a localized surge-like event at the glacier's western margin which drove the formation of ice cliffs from crevassing; these cliffs occur in sets with parallel linear morphologies contrasting with the crescent planform shape of stream-driven cliffs. The development of landscape evolution models may assist in quantifying the total net effect of these processes on steady-state ice cliff coverage and mass balance, contextualizing them with other drivers including supraglacial ponds, differential melt, ice dynamics, and collapse of englacial voids.

Fine Cloud Structures on a Hard Snowball Earth

AbstractEarth may have been globally ice‐covered at least two times during the Cryogenian Period (720–635 Ma). Previous studies showed that clouds could strongly warm a hard snowball Earth and promote its deglaciation. However, the understanding of clouds was largely based on coarse‐resolution global simulations with parameterized convection and clouds, or high‐resolution cloud‐resolving simulations with explicit convection and clouds but limited to a small domain without the effects of large‐scale circulation. Here we present the first global non‐hydrostatic high‐resolution (30 km) simulation to investigate snowball clouds and their radiative effects. We show that spatial‐temporal cloud distributions exhibit clear meanders (patterns of curved lines rather than straight lines along the west‐east direction) and strong variabilities, which result from the tight interactions among the Inter‐Tropical Convergence Zone, Hadley cells, and baroclinic instability. The net cloud radiative effect is around 20 W m−2 in the tropics, consistent with previous global general circulation model simulations.

Climate change could negate U.S. forest ecosystem service benefits gained through reductions in nitrogen and sulfur deposition

Climate change and atmospheric deposition of nitrogen (N) and sulfur (S) impact the health and productivity of forests. Here, we explored the potential impacts of these environmental stressors on ecosystem services provided by future forests in the contiguous U.S. We found that all stand-level services benefitted (+ 2.6 to 8.1%) from reductions in N+S deposition, largely attributable to positive responses to reduced S that offset the net negative effects of lower N levels. Sawtimber responded positively (+ 0.5 to 0.6%) to some climate change, but negatively (− 2.4 to − 3.8%) to the most extreme scenarios. Aboveground carbon (C) sequestration and forest diversity were negatively impacted by all modelled changes in climate. Notably, the most extreme climate scenario eliminated gains in all three services achieved through reduced deposition. As individual tree species responded differently to climate change and atmospheric deposition, associated services unique to each species increased or decreased under future scenarios. Our results suggest that climate change should be considered when evaluating the benefits of N and S air pollution policies on the services provided by U.S. forests.

Effects of internal migrants' health on economic resilience in China's Yangtze River Delta urban agglomeration: moderating effects of basic public health services

IntroductionInternal migrants constitute a significant generality in the socioeconomic development of developing countries. With the frequent occurrence of major public health emergencies, obstacles to labor supply due to health issues among internal migrants not only affect their livelihood stability but also urban economic resilience. Moreover, the design of basic public health service systems tends to favor local residents over internal migrants, further exacerbating the health and employment risks of internal migrants. As a result, urban economic resilience faces significant challenges.ObjectiveThe objective of this study was to deconstruct economic resilience into economic resistance and recovery abilities, investigate the net effect and its heterogeneity of internal migrants' health on economic resilience in China's Yangtze River Delta urban agglomeration (CYRD), and the mediating effect from labor participation rate and labor time supply, as well as the moderating effect of basic public health services.MethodsBased on the China Migrants Dynamic Survey data (CMDS), the study empirically estimated the effects of internal migrants' health on economic resilience in CYRD through microeconometric analysis methods, mediating and moderating effect model.ResultsOur findings indicate that internal migrants' health has a positive effect on economic resilience in CYRD. For each unit increase in migrants' health, it will drive up the average economic resistance ability by 0.0186 and the average recovery ability by 0.0039. Secondly, the net effects of migrants' health on economic resilience show significant structural differences, industry and city heterogeneity. The effect of migrants' health on economic resistance ability is significantly higher than that on economic recovery ability; The effect of migrants' health on economic resilience of the secondary industry is higher than that of the tertiary industry; The cities with high economic resistance and recovery abilities have more prominent positive effect from migrants' health. Thirdly, migrants' health not only has a direct effect on the economic resistance and recovery abilities, but also has a mediating effect on which through labor participation rate and labor time supply.DiscussionEnhancing the accessibility and quality of basic public health services is beneficial for enhancing the positive effects of internal migrants' health on economic resilience.

Diverging phenology of American lobster (Homarus americanus) larvae and their zooplankton prey in a warming ocean

Abstract We build on previous research describing correlative links between changes in the abundance of the copepod Calanus finmarchicus, a foundational zooplankton species of the pelagic food web, and diminishing recruitment of young-of-year American lobster (Homarus americanus) to benthic nurseries in the Gulf of Maine. Using parallel 31-year time series of lobster larvae and zooplankton collected on the New Hampshire coast between 1988 and 2018, we investigated how changes in phenology of stage I larval lobster and their putative copepod prey, C. finmarchicus, affect their temporal overlap and potential to interact during the larval season. We found that over the time series both the lobster egg hatch and first appearance of larvae began earlier in the season, a trend significantly correlated with ocean warming. The last appearance of larvae in late summer has been delayed, however, thereby extending the larval season. Even with the longer larval lobster season, the C. finmarchicus season has increasingly been ending before the peak abundance of stage I lobster larvae. The net effect is a widening mismatch in phenology of the two species, an outcome consistent with the hypothesis that changes in abundance and phenology of C. finmarchicus have contributed to recent declines in lobster recruitment.

Energy services for solar PV projects: Exploring the accessibility and affordability of clean energy for rural China

China's rural solar photovoltaic projects (SPVPs), as an innovative initiative to improve livelihoods through clean energy, have played a positive role in poverty reduction. However, whether this measure can enhance energy services for rural families remains unconfirmed. This paper employs a quasi-experimental method from the perspectives of energy service accessibility and affordability to quantify the net contribution of China's rural SPVPs to enhancing family energy services. The results indicate: (1) SPVPs can significantly improve family energy services, with a net effect of 14.7 % on the energy service accessibility and a net effect of 44.5 % on the energy service affordability. (2) SPVPs can increase the energy consumption capacity, energy supply capacity and energy equipment utilization rate by 2.6 %, 7.1 % and 5 %, respectively. Furthermore, these initiatives can effectively slash the energy costs of rural families by 4.3 %, bolster the energy access affordability by 3.9 %, and catapult energy investments by an impressive 44.9 %. (3) These projects also perform well in the family energy consumption cleanliness. (4) The effect of SPVPs in providing energy services presents a regional difference, with the best performance observed in ‘Type III’ solar resource areas. Meanwhile, the implementation of China's rural SPVPs does not involve “elite capture.”

Abstract PO5-14-01: Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers

Abstract Background: Obesity-associated gut microbiome dysbiosis is thought to increase risk for postmenopausal breast cancer through alteration of estrogen metabolism and an increase in pro-inflammatory microbe abundance. Many studies have reported an increase in the Firmicutes/Bacteroidetes phyla ratio as a biomarker of obesity and is associated with adverse metabolic outcomes. Marine omega-3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids are thought to have favorable metabolic and inflammation resolving properties resulting in reduced risk for several epithelial cancers. One possible mechanism is the effect of EPA and DHA on the gut microbiome. We assessed the effect of weight loss and/or omega-3 supplementation on the gut microbiome and circulating molecular breast cancer risk factors. Methods: 46 peri/postmenopausal overweight and obese women at increased risk for breast cancer were enrolled into a weight-loss intervention and after 2 weeks randomized to 3.25 g/day combined EPA and DHA or placebo (PMC8416797). Fecal samples were collected at 0, 2-weeks and 6-months, with matched fecal samples for all timepoints available for 26 patients. Fecal samples at 6-months were available for 34 patients. 12M read depth metagenomic sequencing was performed on DNA isolated from feces to determine shifts in the gut microbiome. Fasting and non-fasting blood was also collected for circulating biomarker analysis. Body composition by DXA scan were also performed at baseline and 6-month time points. Results: Mean baseline BMI was 32 kg/m2. There was no significant difference between arms in age, baseline BMI, % body fat, or baseline Firmicutes/Bacteroidetes ratio. We identified gut microbiota species (A. hadrus and P. faecium) that correlated with metabolic parameters (% body fat, adiponectin/leptin ratio, and fasting insulin), species (P. dorei and B. ovatus) that correlated with estradiol levels, and mucin-degrading species (D. formicigenerans and R. gnavus) whose abundance correlated with inflammation (as measured by circulating monocyte-chemoattractant protein 1 (MCP-1)). Median 6-month weight change for all randomized subjects was -10% from baseline. Favorable change in the Firmicutes/Bacteroidetes ratio was associated both with the degree of weight loss and with omega-3 supplementation, although significant species modification differed between weight loss and omega-3 PUFA groups. Women with both >10% weight loss and omega-3 supplementation had a significantly reduced Firmicutes abundance and lower Firmicute/Bacteroidetes ratio than other groups. Species abundance shifts appear to differ between weight loss and omega-3 supplementation with 3 species modified by weight loss and 12 species shifted by omega-3 PUFA administration. Omega-3 PUFA supplementation significantly reduced proportional abundance of Dorea formicigenerans, which was a microbe associated with inflammation. Conclusions: Omega-3 supplementation at 3.25 g/day compared to placebo had a greater net effect on changing the gut microbiome in overweight and obese women at increased risk for breast cancer undergoing a weight loss intervention. Change in the gut microbiome may serve as a useful response biomarker in Phase II prevention trials of omega-3 fatty acid and weight loss. Citation Format: Katherine L. Cook, Erin Giles, Amy Kreutzjans, Shahid Umar, Christie Befort, Bruce Kimler, Stephen Hursting, Carol Fabian. Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-14-01.

Effect of anisotropic thermal transport on tearing mode stability in negative versus positive triangularity plasmas

The combined effects of anisotropic thermal transport and the plasma shaping, including negative triangularity, on the n = 1 (n is the toroidal mode number) tearing mode (TM) stability are numerically investigated utilizing the MARS-F code [Liu et al., Phys. Plasmas 7, 3681–3690 (2000)]. While varying the plasma boundary triangularity, the TM stability is found to be dictated by the competing effects of the Shafranov shift induced stabilization and the bad-curvature induced destabilization. The negative triangularity shape increases the Shafranov shift (stabilizing) in the plasma core but also enlarges bad-curvature regions (destabilizing) near the plasma edge, with the net effect being largely destabilizing for the TM as compared to the positive triangularity counter-part. Large negative triangularity however can also lead to more stabilization for the plasma core-localized TM. Anisotropic thermal transport reduces the stabilizing effect on the TM associated with the favorable averaged curvature, resulting in more unstable core-localized TMs in both negative and positive triangularity plasmas. But the opposite effect can also take place for the edge-localized TM in finite-pressure plasmas with negative triangularity.

LNG Freight Rate and LNG Price, Carbon Price, Geopolitical risk: A Dynamic Connectedness Analysis

With the change in energy structure, the world's demand for natural gas is increasing, and the LNG shipping market is also gradually expanding. This paper studies the time-varying connectedness between LNG freight rates and natural gas prices, geopolitical risk, and carbon prices in time and frequency domain with TVP-VAR-DY spillover index and TVP-VAR-BK spillover index respectively. Both global market and regional markets are considered in this research. This research draws the following conclusions: firstly, in this system, the short-term connectedness is the largest, followed by the long-term connectedness. Secondly, multi-month freight rates is crucial in the system. Thirdly, the net spillover effect from geopolitical risk to freight rate only appears in the short term and it’s very small. Just considering the one-way connectedness, the importer’s geopolitical risk transmits most short-term shocks and the exporter’s geopolitical risk transmits most medium-term shocks. Finally, after the carbon price rose in the fourth stage of EU ETS, it became the transmitter of shocks to LNG freight rates in the global market and Australia-Japan market. It also received less shocks from LNG freight rates in the U.S.-Europe market. Based on these findings, we provide guidance for interested agents in the end.

Are digital servitization-based Circular Economy business models sustainable? A systemic what-if simulation model

Manufacturing companies are struggling with the implementation of Circular Economy, especially due to the uncertainty regarding its potential sustainability benefits. In particular, and despite digital servitization is advocated by several studies as a way to achieve environmental gains, circular business models based on digital servitization are not always sustainable due to burden shifting and unexpected consequences which are difficult to assess before implementation. This is particularly relevant for the Electrical and Electronics Equipment industry, which suffers structural weaknesses such as the dependance on critical raw materials and an increasing waste generation. However, literature lacks models and tools able to address the complexity inherent in the systemic micro-macro perspective envisioned by Circular Economy, while studies that quantitatively assess the sustainability impacts and trade-offs of digital servitization-based circular scenarios are limited. This article aims to develop a better understanding of how the sustainability impacts of circular and servitized scenarios can be assessed and quantified at the economic, environmental, and social level, adopting a systemic perspective through the development of a what-if simulation model. The model is implemented in a spreadsheet tool and applied to a digital servitization-based Circular Economy scenario inspired by the case of a company offering long-lasting, high-efficient washing machines as-a-service. Results show that digital servitization can actually lead to a win-win-win situation with net positive effects to the environment, the society, and the economy. This result is based on the joint application of product design for digitalization and life extension, pay-per-use business models, and product reuse. These results are robust within a significant range of key parameters values. Practitioners and policymakers may use the model to support the evaluation of different circular and servitized scenarios before implementation.

Feasibility of replacing face-to-face with telephone interviews for the World Mental Health Qatar survey during the COVID-19 pandemic.

We investigated the feasibility of replacing face-to-face with telephone interviews conducted as part of the World Mental Health Qatar (WMHQ) survey and discuss the main methodological changes across the two pilots that were subsequently implemented in the full-scale WMHQ telephone survey. We assessed the net mode effect by comparing the lifetime prevalence estimates of the main mental disorder classes (mood and anxiety disorders) and a number of disorders across the two survey pilots conducted prior to and post-pandemic. The main differences in terms of methodology for both pilots stemmed from differences in the survey mode, including questionnaire length, study recruitment method, and fielding team size and structure. These factors influenced response rates and costs. However, the lifetime prevalence estimates and other key indicators of survey results did not differ across modes. Our findings confirm the comparability of data collected via telephone and face-to-face modes, supporting the adoption of telephone surveys for future mental health studies, particularly in the context of pandemics. They also confirm the feasibility of changing or mixing modes depending on field conditions in future psychiatric epidemiological research.

A decade of Eurasian integration: An ex-post non-parametric assessment of the Eurasian economic union

This paper provides a sound ex-post evaluation of the impact of the Eurasian integration on member countries’ bilateral trade after a decade of implementation. We overcome the main limitations of current empirical analyses on the effects of trade agreements, namely the aggregation of tariff and non-tariff barriers and the likely self-selection bias, by applying a non-parametric method specifically designed to fully exploit time-series cross-sectional data. We thus compare the trade flows of the member countries in the Eurasian agreement with the exporter-importer pairs located in the Eurasian continent most similar in terms of pre-treatment trends and features. Our results confirm the previous literature about the lack of a significant impact of the Eurasian customs union, but find more positive net effects of the more recent integration steps. Our results ask for conveying additional efforts to complete the Eurasian integration and let its member countries fully benefit from its hoped-for long-term effects.

Impacts assessment of nitrification inhibitors on U.S. agricultural emissions of reactive nitrogen gases

Fertilizer-intensive agriculture leads to emissions of reactive nitrogen (Nr), posing threats to climate via nitrous oxide (N2O) and to air quality and human health via nitric oxide (NO) and ammonia (NH3) that form ozone and particulate matter (PM) downwind. Adding nitrification inhibitors (NIs) to fertilizers can mitigate N2O and NO emissions but may stimulate NH3 emissions. Quantifying the net effects of these trade-offs requires spatially resolving changes in emissions and associated impacts. We introduce an assessment framework to quantify such trade-off effects. It deploys an agroecosystem model with enhanced capabilities to predict emissions of Nr with or without the use of NIs, and a social cost of greenhouse gas to monetize the impacts of N2O on climate. The framework also incorporates reduced-complexity air quality and health models to monetize associated impacts of NO and NH3 emissions on human health downwind via ozone and PM. Evaluation of our model against available field measurements showed that it captured the direction of emission changes but underestimated reductions in N2O and overestimated increases in NH3 emissions. The model estimated that, averaged over applicable U.S. agricultural soils, NIs could reduce N2O and NO emissions by an average of 11% and 16%, respectively, while stimulating NH3 emissions by 87%. Impacts are largest in regions with moderate soil temperatures and occur mostly within two to three months of N fertilizer and NI application. An alternative estimate of NI-induced emission changes was obtained by multiplying the baseline emissions from the agroecosystem model by the reported relative changes in Nr emissions suggested from a global meta-analysis: −44% for N2O, −24% for NO and +20% for NH3. Monetized assessments indicate that on an annual scale, NI-induced harms from increased NH3 emissions outweigh (8.5–33.8 times) the benefits of reducing NO and N2O emissions in all agricultural regions, according to model-based estimates. Even under meta-analysis-based estimates, NI-induced damages exceed benefits by a factor of 1.1–4. Our study highlights the importance of considering multiple pollutants when assessing NIs, and underscores the need to mitigate NH3 emissions. Further field studies are needed to evaluate the robustness of multi-pollutant assessments.

Bio-efficacy of Olyset® Plus, PermaNet® 3.0 and Interceptor® G2 on pyrethroid-resistant populations of Anopheles gambiae s.l. prior to the June 2023 net distribution campaign in Benin, West Africa

BackgroundThis study investigates the effectiveness of new-generation mosquito nets, like Olyset® Plus and PermaNet® 3.0, and dual-action nets such as Interceptor® G2, against pyrethroid-resistant Anopheles gambiae mosquitoes following the 2023 mass distribution of long-lasting insecticidal nets in Benin.MethodsWe tested wild mosquito populations from six communes in Benin against various pyrethroid (permethrin 0.75%, alphacypermethrin 0.05%, and deltamethrin 0.05%) using WHO tube tests. Additionally, we exposed mosquitoes to chlorfenapyr 100 µg/ml using the CDC bottle bioassay method. A subset of mosquitoes underwent biochemical and PCR tests to check the overexpression of metabolic enzymes and the Kdr L1014F mutation. We evaluated the effectiveness of Olyset® Plus, PermaNet® 3.0, and Interceptor® G2 nets using cone and tunnel tests on both laboratory and field populations of An. gambiae.ResultsOverall, the highest mortality rate was 60% with pyrethroid and 98 to100% with chlorfenapyr. In cone tests, all three types of nets induced mortality rates above 80% in the susceptible laboratory strain of An. gambiae. Notably, Olyset® Plus showed the highest mortality rates for pyrethroid-resistant mosquitoes in cone tests, ranging from 81.03% (95% CI: 68.59–90.13) in Djougou to 96.08% (95% CI: 86.54–99.52) in Akpro-Missérété. PermaNet® 3.0 had variable rates, from 42.5% (95% CI: 27.04–59.11) in Djougou to 58.54% (95% CI: 42.11–73.68) in Porto-Novo. However, revealed good results for Interceptor® G2, with 94% (95% CI: 87.40–97.77) mortality and 89.09% blood sampling inhibition in local populations of An. gambiae. In comparison, Interceptor® had lower rates of 17% (95% CI: 10.23–25.82) and 60%, respectively.ConclusionThese results suggest that tunnel tests are effective for evaluating dual-active ingredient nets. Additionally, Interceptor® G2 and PBO nets like Olyset® Plus could be considered as alternatives against pyrethroid-resistant mosquitoes.

Saturated fatty acids inhibit unsaturated fatty acid induced glucose uptake involving GLUT10 and aerobic glycolysis in bovine granulosa cells

Fatty acids have been shown to modulate glucose metabolism in vitro and in vivo. However, there is still a need for substantial evidence and mechanistic understanding in many cell types whether both saturated and unsaturated fatty acids (SFAs and UFAs) pose a similar effect and, if not, what determines the net effect of fatty acid mixes on glucose metabolism. In the present study, we asked these questions by treating granulosa cells (GCs) with the most abundant non-esterified fatty acid species in bovine follicular fluid. Results revealed that oleic and alpha-linolenic acids (UFAs) significantly increased glucose consumption compared to palmitic and stearic acids (SFAs). A significant increase in lactate production, extracellular acidification rate, and decreased mitochondrial activity indicate glucose channeling through aerobic glycolysis in UFA treated GCs. We show that insulin independent glucose transporter GLUT10 is essential for UFA driven glucose consumption, and the induction of AKT and ERK signaling pathways necessary for GLUT10 expression. To mimic the physiological conditions, we co-treated GCs with mixes of SFAs and UFAs. Interestingly, co-treatments abolished the UFA induced glucose uptake and metabolism by inhibiting AKT and ERK phosphorylation and GLUT10 expression. These data suggest that the net effect of fatty acid induced glucose uptake in GCs is determined by SFAs under physiological conditions.

Interchangeability of multi-decade skin and surface air temperature trends over land in models

Satellite land surface temperature (Ts ) records have now reached 20+ year length, but their trends may differ from historical records built from in-situ measurements of near-surface air temperature (Tas ). In the ERA5 reanalysis, 60° S–60° N land Ts and Tas trends can differ by up to ±0.06 °C decade−1 over 20 years, depending on the period, or more on smaller spatial scales. Here I use 1979–1998 outputs from ACCESS1-0 climate model simulations with prescribed land Ts to understand changes in Ts and Tas . CO2’s effective radiative forcing causes adjustments that warm Tas relative to Ts . In ACCESS1-0, vegetation enhances the adjustments to CO2 over land. Meanwhile, feedbacks in ACCESS1-0 oppose the adjustments, resulting in small long-term net effects on global temperature estimates. In coupled simulations from other models, there is no agreement on whether Ts or Tas warms more and the most extreme case shows global long-term differences of just 5% between land Ts or land Tas trends. The results contrast with over-ocean behavior where adjustments and feedbacks reinforce each other, and drive larger long-term Tas warming relative to Ts across all models.

Pyrethroid resistance and gene expression profile of a new resistant An. gambiae colony from Uganda reveals multiple resistance mechanisms and overexpression of Glutathione-S-Transferases linked to survival of PBO-pyrethroid combination

Background The effectiveness of long-lasting insecticidal nets (LLINs) are being threatened by growing resistance to pyrethroids. To restore their efficacy, a synergist, piperonyl butoxide (PBO) which inhibits cytochrome P450s has been incorporated into pyrethroid treated nets. A trial of PBO-LLINs was conducted in Uganda from 2017 and we attempted to characterize mechanisms of resistance that could impact intervention efficacy. Methods We established an Anopheles gambiae s.s colony in 2018 using female mosquitoes collected from Busia district in eastern Uganda. We first assessed the phenotypic resistance profile of this colony using WHO tube and net assays using a deltamethrin dose-response approach. The Busia colony was screened for known resistance markers and RT-qPCR targeting 15 genes previously associated with insecticide resistance was performed. Results The Busia colony had very high resistance to deltamethrin, permethrin and DDT. In addition, the colony had moderate resistance to alpha-cypermethrin and lambda-cyhalothrin but were fully susceptible to bendiocarb and fenitrothion. Exposure to PBO in combination with permethrin and deltamethrin resulted in higher mortality rates in both net and tube assays, with a higher mortality observed in net assays than tube assays. The kdr marker, Vgsc-995S was at very high frequency (91.7-98.9%) whilst the metabolic markers Coeae1d and Cyp4j5-L43F were at very low (1.3% - 11.5%) and moderate (39.5% - 44.7%) frequencies respectively. Our analysis showed that gene expression pattern in mosquitoes exposed to deltamethrin, permethrin or DDT only were similar in comparison to the susceptible strain and there was significant overexpression of cytochrome P450s, glutathione-s-transferases (GSTs) and carboxyl esterases (COEs). However, mosquitoes exposed to both PBO and pyrethroid strikingly and significantly only overexpressed closely related GSTs compared to unexposed mosquitoes while major cytochrome P450s were underexpressed. Conclusions The high levels of pyrethroid resistance observed in Busia appears associated with a wide range of metabolic gene families.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care.

De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients. Cumulative immunosuppression has been shown to contribute to post-transplant malignancy (PTM) risk. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net effect of immunosuppression. Calcineurin inhibitors such as tacrolimus may promote tumourigenesis, whereas mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, may limit tumour progression. Liver transplantation (LT) is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable, which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort. However, there is limited clinical data on this subject in both LT and other solid organ transplant recipients. To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation. A literature search was conducted using MEDLINE and Embase databases using the key terms "solid organ transplantation", "tacrolimus", "mycophenolic acid", and "carcinogenicity", in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022. Related terms, synonyms and explosion of MeSH terms, Boolean operators and truncations were also utilised in the search. Reference lists of retrieved articles were also reviewed to identify any additional articles. Excluding duplicates, abstracts from 1230 records were screened by a single reviewer, whereby 31 records were reviewed in detail. Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria. A total of 6 studies were included in this review. All studies were large population registries or cohort studies, which varied in transplant era, type of organ transplanted and immunosuppression protocol used. Overall, there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation. Furthermore, no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients. The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies, and its application in solid organ transplantation, is yet to be confirmed in clinical studies. Thus, the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Learning generatively to facilitate marketing innovation of international joint ventures in emerging markets

PurposeThis study aims to investigate a mediation model in which generative learning positively affects marketing innovation and both organizational control and relationship openness mediate the relationship between learning intent and generative learning of international joint ventures (IJVs) in emerging markets. We also decipher the degree of necessity of these factors for generative learning and of generative learning for marketing innovation.Design/methodology/approachA sample of 181 marketing managers of IJVs in Vietnam, an emerging market, was surveyed to collect data. Partial least squares structural equation modeling (PLS-SEM) was employed to test the net effect, and necessary condition analysis (NCA) was used to decipher the degree of necessity.FindingsThe PLS-SEM results demonstrate that the effect of learning intent on generative learning is fully mediated by organizational control and relationship openness, which in turn leads to marketing innovation. The NCA findings reveal that all three factors, namely learning intent, organizational control and relationship openness, serve as necessary conditions for generative learning. However, generative learning does not play the role of a necessary condition for marketing innovation.Practical implicationsThe study findings suggest that IJVs in emerging markets should pay attention not only to the net effects of those factors but also to their degrees of necessity for generative learning in order to achieve marketing innovation.Originality/valueThe study contributes to the literature by confirming the mediating roles of organizational control and relationship openness in the relationship between learning intent and generative learning. Furthermore, it is among the first to decipher the degrees of necessity of these factors for generative learning and of generative learning for the marketing innovation of IJVs in emerging markets.